H.sub.3 receptor sites are known and are of current interest to those skilled in the art as a therapeutic target. U.S. Pat. No. 4,767,778 (Arrang et al) discloses certain imidazoles that behave as agonists of the H.sub.3 receptors in rat brain. European Patent Application No. 0 420 396 A2 (Smith Kline & French Laboratories Limited) and Howson et al., (Bioorg. & Med. Chem. Letters, (1992), Vol. 2 No. 1, pp. 77-78) describe imidazole derivatives having an amidine group as H.sub.3 agonists. Van der Groot et al. (Eur. J. Med. Chem. (1992) Vol. 27, pp. 511-517) describe isothiourea analogs of histamine as potent agonists or antagonists of the histamine-H.sub.3 receptor, and these isothiourea analogs of histamine overlap in part with those of the two references cited above. Clapham et al. ["Ability of Histamine-H.sub.3 Receptor Antagonists to Improve Cognition and to Increase Acetylcholine Release in vivo in the Rat", British Assn. for Psychopharmacology, Jul. 25-28 (1993), reported in J. Psychopharmacol. (Abstr. Book), A17] describe the ability of histamine-H.sub.3 receptor antagonists to improve cognition and to increase release of acetylcholine in vivo in the rat. Clapham et al. ["Ability of the selective Histamine-H.sub.3 Receptor Antagonist Thioperamide to improve Short-term Memory and Reversal Learning in the Rat", Brit. J. Pharm. Suppl., 1993, 110, Abstract 65P] present results showing that thioperamide can improve short-term memory and reversal learning in the rat and implicate the involvement of H.sub.3 receptors in the modulation of cognitive function. Yokoyama et al. ["Effect of Thioperamide, a Histamine-H.sub.3 Receptor Antagonist, on --Electrically Induced Convulsions in Mice", Eur. J. Pharmacol., (1993), Vol. 234, pp. 129-133] report how thioperamide decreased the duration of each phase of convulsion and raised the electroconvulsive threshold, and go on to suggest that these and other findings support the hypothesis that the central histaminergic system is involved in the inhibition of seizures. International Patent Publication No. WO 9301812-Al (SmithKline Beecham PLC) describes the use of S-[3-(4(5)-imidazolyl)propyl]isothiourea as a histamine-H.sub.3 antagonist, especially for treating cognitive disorders, e.g. Alzheimer's disease and age-related memory impairment. Schlicker et al. ["Novel Histamine-H.sub.3 Receptor Antagonists: Affinities in an H.sub.3 Receptor Binding Assay and Potencies in Two Functional H.sub.3 Receptor Models", British J. Pharmacol., (1994), Vol. 112, 1043-1048] describe a number of imidazolylalkyl compounds wherein the imidazolylalkyl group is bonded to a guanidine group, an ester group, an amide group, a thioamide group and a urea group, and compared these to thioperamide. Leurs et al. ["The Histamine-H.sub.3 -receptor: A Target for Developing New Drugs", Progr. Drug Res. (1992), Vol. 39, pp. 127-165] and Lipp et al. ["Pharmacochemistry of H.sub.3 -receptors" in The Histamine Receptor, eds.: Schwartz and Haas, Wiley-Liss, New York (1992), pp. 57-72] review a variety of synthetic H.sub.3 receptor antagonists, and Lipp et al. (ibid.) have proposed the necessary structural requirements for an H.sub.3 receptor antagonist.
WO 95/14007 claims H.sub.3 receptor antagonists of the formula ##STR2##
wherein A, m, n, R.sup.1 and R.sup.2 are defined therein. The compounds are disclosed as being useful for treating various disorders, in particular such caused by allergy-induced responses.
WO 93/12093 discloses imidazolylmethyl piperazines and diazepines as H.sub.3 antagonists. U.S. patent application, Ser. No. 08/965,754, filed Nov. 7, 1997, discloses imidazolylalkyl substituted heterocyclic ring compounds as H.sub.3 receptor antagonists. U.S. patent application, Ser. No. 08/966,344, filed Nov. 7, 1997, discloses phenylalkylimidazoles as H.sub.3 receptor antagonists.
Reference is also made to U.S. application, Ser. No. 08/689,951, filed Aug. 16, 1996 which claims the combined use of a histamine-H, receptor antagonist and a histamine-H.sub.3 receptor antagonist for treatment of allergy-induced airway responses.
Reference is also made to J. R. Bagley et al, Journal of Medicinal Chemistry, (1991), Vol. 34, 827-841, which discloses, among others, N-(imidazolylalkyl) substituted cyclic amine compounds useful as analgesics such as the amine compound with the formula: ##STR3##
Pending U.S. patent application, Ser. No. 09/173,642, filed Oct. 16, 1998 (R. Wolin et al), discloses N-(imidazolylalkyl) substituted cyclic amine compounds having H.sub.3 antagonist activity.
In view of the art's interest in compounds which affect the H.sub.3 receptor, novel compounds having agonist or antagonist activity on H.sub.3 receptors would be a welcome contribution to the art. This invention provides just such a contribution by providing novel compounds having H.sub.3 agonist or antagonist activity.